AB0648 CYTOKINE AND CARDIOVASCULAR BIOMARKER PROFILES IN SOUTH AFRICAN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS WITH SUBCLINICAL CARDIOVASCULAR INVOLVEMENT CHARACTERISED BY MULTIMODAL IMAGING
Authors: T. M. Bana, M. Shey, P. Samuels, S. Jermy, S. Kraus, N. Ntusi
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in systemic lupus erythematosus (SLE). Traditional risk tools underestimate CVD risk in young SLE patients. Identification of biomarkers may have utility in predicting CV involvement in SLE. <h3>Objectives</h3> To profile cytokine and CV biomarkers, associated with immune activation, fibrosis, CV dysfunction, and myocardial and vascular injury, in ambulatory South African SLE patients with subclinical CV involvement. <h3>Methods</h3> SLE patients, without known CVD, were recruited from rheumatology clinics at an academic hospital in Cape Town, and compared to controls matched for age, gender and ethnicity. All patients underwent echocardiography, carotid Duplex ultrasound, ankle brachial index and cardiovascular magnetic resonance (CMR) to characterise early CV involvement. Blood samples were obtained and stored at -80°C. Commercially available sandwich high sensitivity (hs) ELISA and Luminex multiplex bead assays were performed according to manufacturer's protocols to quantify biomarkers. Continuous variables were compared using Independent Samples t Test or Mann Whitney U Test. Regression analysis determined the strength and direction of associations between variables using Spearman's correlation co-efficient. <h3>Results</h3> 49 SLE patients attending routine outpatient follow-up, and 24 controls, were enrolled. SLE patients were 35±9 years old; 90% were women; and predominantly of mixed (69%) or black African (27%) ancestry. Median disease duration was 5 (IQR:3-8) years and patients had moderate disease activity (SLEDAI-2K=7 [IQR:4-12]) and low damage scores (SLICC-DI=1 [IQR:0-1]). On CMR, a substantial proportion (86%) of SLE patients were found to have subclinical CVD, with predominantly myocardial (78%) and pericardial (27%) involvement. We observed that despite having low C-reactive protein levels (2.54mg/L vs 2.90mg/L, p=0.36), compared to controls, SLE patients had significantly increased cytokine responses, including IL 1B, IL 6, TNFa &amp; IFNg levels (p&lt;0.001 for all, Table 1). Markers of fibrosis were significantly different in SLE, showing elevations in TIMP 1 (p&lt;0.001) and galectin-3 (p=0.016), and decreased levels of MMP-9 (p&lt;0.001). On regression analysis, MMP 9 showed an inverse relationship to all CMR parameters of myocardial fibrosis, including native myocardial T1 time, extracellular volume fraction and late gadolinium enhancement percentage (Figure 1), albeit with low co-efficient values. There were no significant correlations between hs troponin T, N-terminal prohormone of brain natriuretic peptide (NT proBNP) and soluble ST2 with parameters of myocardial dysfunction nor did cytokines measured correlate with indices of disease activity. In addition, VCAM 1, a marker of vascular injury was significantly elevated in SLE (p&lt;0.001) but did not correlate with carotid intima media thickness or ankle brachial indices. Similar to previous studies, adiponectin showed an inverse correlation with BMI, but did not correlate with any manifestations of subclinical CVD. <h3>Conclusion</h3> In this cohort of young South African patients with stable SLE and subclinical CVD, we found evidence of ongoing immune activation. Low MMP 9 levels may be an early signal of myocardial disease. Plasma biomarkers may be useful in predicting CVD in SLE but larger prospective studies in SLE patients with CVD are needed. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.